Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

Gregory T. Kennedy; Feredun S. Azari; Elizabeth Bernstein; Bilal Nadeem; Ashley Chang; Alix Segil; Sean Carlin; Neil T. Sullivan; Emmanuel Encarnado; Charuhas Desphande; Sumith Kularatne; Pravin Gagare; Mini Thomas; John C. Kucharczuk; Gaetan Christien; Francois Lacombe; Kaela Leonard; Philip S. Low; Aline Criton; Sunil Singhal

doi:10.1038/s41467-022-30265-z

Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

Gregory T. Kennedy, Feredun S. Azari, Elizabeth Bernstein, Bilal Nadeem, Ashley Chang, Alix Segil, Sean Carlin, Neil T. Sullivan, Emmanuel Encarnado, Charuhas Desphande, Sumith Kularatne, Pravin Gagare, Mini Thomas, John C. Kucharczuk, Gaetan Christien, Francois Lacombe, Kaela Leonard, Philip S. Low, Aline Criton, Sunil Singhal

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

Original language	English (US)
Article number	2711
Pages (from-to)	2711
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30265-z
State	Published - May 17 2022

Keywords

Biopsy
Endoscopy
Humans
Lasers
Microscopy, Confocal/methods
Pancreatic Neoplasms/pathology

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-022-30265-z

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Kennedy, G. T., Azari, F. S., Bernstein, E., Nadeem, B., Chang, A., Segil, A., Carlin, S., Sullivan, N. T., Encarnado, E., Desphande, C., Kularatne, S., Gagare, P., Thomas, M., Kucharczuk, J. C., Christien, G., Lacombe, F., Leonard, K., Low, P. S., Criton, A., & Singhal, S. (2022). Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy. Nature Communications, 13(1), 2711. Article 2711. https://doi.org/10.1038/s41467-022-30265-z

Kennedy, GT, Azari, FS, Bernstein, E, Nadeem, B, Chang, A, Segil, A, Carlin, S, Sullivan, NT, Encarnado, E, Desphande, C, Kularatne, S, Gagare, P, Thomas, M, Kucharczuk, JC, Christien, G, Lacombe, F, Leonard, K, Low, PS, Criton, A & Singhal, S 2022, 'Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy', Nature Communications, vol. 13, no. 1, 2711, pp. 2711. https://doi.org/10.1038/s41467-022-30265-z

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title = "Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy",

abstract = "Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.",

keywords = "Biopsy, Endoscopy, Humans, Lasers, Microscopy, Confocal/methods, Pancreatic Neoplasms/pathology",

author = "Kennedy, {Gregory T.} and Azari, {Feredun S.} and Elizabeth Bernstein and Bilal Nadeem and Ashley Chang and Alix Segil and Sean Carlin and Sullivan, {Neil T.} and Emmanuel Encarnado and Charuhas Desphande and Sumith Kularatne and Pravin Gagare and Mini Thomas and Kucharczuk, {John C.} and Gaetan Christien and Francois Lacombe and Kaela Leonard and Low, {Philip S.} and Aline Criton and Sunil Singhal",

note = "Funding Information: The research was funded in part by NIH Grants F32 CA254210-01 (G.T.K.) and R01 CA193556 (S.S.); American Philosophical Society Daland Fellowship in Clinical Investigation (G.T.K.); Thoracic Surgery Foundation Resident Research Scholarship (F.S.A.); and the State of Pennsylvania Health Research Formula Fund Grant (S.S.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

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doi = "10.1038/s41467-022-30265-z",

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T1 - Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

AU - Kennedy, Gregory T.

AU - Azari, Feredun S.

AU - Bernstein, Elizabeth

AU - Nadeem, Bilal

AU - Chang, Ashley

AU - Segil, Alix

AU - Carlin, Sean

AU - Sullivan, Neil T.

AU - Encarnado, Emmanuel

AU - Desphande, Charuhas

AU - Kularatne, Sumith

AU - Gagare, Pravin

AU - Thomas, Mini

AU - Kucharczuk, John C.

AU - Christien, Gaetan

AU - Lacombe, Francois

AU - Leonard, Kaela

AU - Low, Philip S.

AU - Criton, Aline

AU - Singhal, Sunil

N1 - Funding Information: The research was funded in part by NIH Grants F32 CA254210-01 (G.T.K.) and R01 CA193556 (S.S.); American Philosophical Society Daland Fellowship in Clinical Investigation (G.T.K.); Thoracic Surgery Foundation Resident Research Scholarship (F.S.A.); and the State of Pennsylvania Health Research Formula Fund Grant (S.S.). Publisher Copyright: © 2022, The Author(s).

PY - 2022/5/17

Y1 - 2022/5/17

N2 - Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

AB - Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

KW - Biopsy

KW - Endoscopy

KW - Humans

KW - Lasers

KW - Microscopy, Confocal/methods

KW - Pancreatic Neoplasms/pathology

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JF - Nature Communications

IS - 1

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ER -

Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

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